tbuckley/cabot-search huggingface dataset:
Early-Onset Cancer in the Gastrointestinal Tract Is on the Rise—Evidence and Implications
Authors: Irit Ben-Aharon, Hanneke W.M. van Laarhoven, Elisa Fontana, Radka Obermannova, Magnus Nilsson, Florian Lordick
Journal: Cancer Discovery (2023)

Epidemiologic data indicate a significant increase in the incidence of colorectal cancer in younger populations in the past three decades. Moreover, recent evidence also demonstrates a similar trend in gastric, pancreatic, and biliary tract cancers. A majority of these early-onset cases are sporadic and lack hereditary or familial background, implying a potential key role for behavioral, lifestyle, nutritional, microbial, and environmental factors. This review explores the current data on early-onset gastrointestinal cancer, exploring the etiology, unique treatment considerations for this population, future challenges, as well as implications for research and practice. The worrisome trend of an increasing incidence of early-onset gastrointestinal cancers appears to be correlated with nonhereditary etiologies in which behavioral, lifestyle, nutritional, microbial, and environmental factors, as well as host mechanisms, may play a key role. Further epidemiologic and pathogenetic research is urgently needed to better understand the underlying mechanisms and to develop preventive strategies and tailored early detection. Young patients with gastrointestinal cancer face unique challenges and unmet needs. These must be addressed in the future management of the disease to minimize treatment-related somatic morbidity and prevent psychosocial sequelae.
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger — United States, 2023
Authors: A. Patricia Wodi, Neil Murthy, Veronica McNally, Sybil Cineas, Kevin Ault
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

At its October 2022 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger, United States, 2023. The 2023 child and adolescent immunization schedule, available on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules), summarizes ACIP recommendations, including several changes from the 2022 immunization schedule† on the cover page, tables, notes, and appendix. Health care providers are advised to use the tables, notes, and appendix together to determine recommended vaccinations for patient populations. This immunization schedule is recommended by ACIP (https://www.cdc.gov/vaccines/acip) and approved by CDC (https://www.cdc.gov), the American Academy of Pediatrics (https://www.aap.org), the American Academy of Family Physicians (https://www.aafp.org), the American College of Obstetricians and Gynecologists (http://www.acog.org), the American College of Nurse-Midwives (https://www.midwife.org), the American Academy of Physician Associates (https://www.aapa.org), and the National Association of Pediatric Nurse Practitioners (https://www.napnap.org).
Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth
Authors: Alan T.N. Tita, Waldemar A. Carlo, Elizabeth M. McClure, Musaku Mwenechanya, Elwyn Chomba, Jennifer J. Hemingway-Foday, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard Derman, Adrien Lokangaka, Antoinette Tshefu, Melissa Bauserman, Carl Bose, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osayame A. Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam S. Tikmani, Sarah Saleem, Robert L. Goldenberg, Sk M. Billah, Ruth Lennox, Rashidul Haque, William Petri, Lester Figueroa, Manolo Mazariegos, Nancy F. Krebs, Janet L. Moore, Tracy L. Nolen, Marion Koso-Thomas
Journal: New England Journal of Medicine (2023)

The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.
IL-1 receptor–associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy
Authors: Gürcan Tunalı, Marta Rúbies Bedós, Divya Nagarajan, Patrik Fridh, Irineos Papakyriacou, Yumeng Mao
Journal: Journal of Clinical Investigation (2023)

Inflammatory mediators released by cancer cells promote the induction of immune suppression and tolerance in myeloid cells. IL-1 receptor–associated kinase-3 (IRAK3) is a pseudokinase that inhibits IL-1/TLR signaling, but its role in patients treated with immune checkpoint blockade (ICB) therapy remains unclear. Using RNA-Seq data from the IMvigor210 trial, we found that tumors with high IRAK3 expressions showed enriched antiinflammatory pathways and worse clinical response to ICB therapy. Upon IRAK3 protein deletion with CRISPR/Cas9, primary human monocytes displayed altered global protein expression and phosphorylation in quantitative proteomics and released more proinflammatory cytokines in response to stimulation. Bone marrow–derived macrophages from an IRAK3 CRISPR KO mouse model demonstrated a proinflammatory phenotype and enhanced sensitivity to TLR agonists compared with WT cells. IRAK3 deficiency delayed the growth of carcinogen-induced and oncogene-driven murine cancer cells and induced enhanced activation in myeloid cells and T cells. Upon ICB treatment, IRAK3-KO mice showed enrichment of TCF1+PD-1+ stem-like memory CD8+ T cells and resulted in superior growth inhibition of immunologically cold tumors in vivo. Altogether, our study demonstrated what we believe to be a novel cancer-driven immune tolerance program controlled by IRAK3 in humans and mice and proposed its suitability as an immunotherapy target.
A pilot sentinel surveillance system to monitor treatment and treatment outcomes of chronic hepatitis B and C infections in clinical centres in three European countries, 2019
Authors: Anthony Nardone, Lina Nerlander, Erika Duffell, Marta Valenciano, Maria Buti, Cristina Marcos-Fosch, Tatjana Nemeth-Blažić, Odette Popovici, Adriana Vince, Petruta Violeta Filip, Tajana Filipec, Mirjana Lana Kosanović Ličina, Boris Luksic, Diana Nonković, Corina Silvia Pop, Fabiana Radu, Irina Teodorescu, Adriana Violeta Topan
Journal: Eurosurveillance (2023)

Background The World Health Organization European Action Plan 2020 targets for the elimination of viral hepatitis are that &gt; 75% of eligible individuals with chronic hepatitis B (HBV) or hepatitis C (HCV) are treated, of whom &gt; 90% achieve viral suppression. Aim To report the results from a pilot sentinel surveillance to monitor chronic HBV and HCV treatment uptake and outcomes in 2019. Methods We undertook retrospective enhanced data collection on patients with a confirmed chronic HBV or HCV infection presenting at one of seven clinics in three countries (Croatia, Romania and Spain) for the first time between 1 January 2019 and 30 June 2019. Clinical records were reviewed from date of first attendance to 31 December 2019 and data on sociodemographics, clinical history, laboratory results, treatment and treatment outcomes were collected. Treatment eligibility, uptake and case outcome were assessed. Results Of 229 individuals with chronic HBV infection, treatment status was reported for 203 (89%). Of the 80 individuals reported as eligible for treatment, 51% (41/80) were treated of whom 89% (33/37) had achieved viral suppression. Of 240 individuals with chronic HCV infection, treatment status was reported for 231 (96%). Of 231 eligible individuals, 77% (179/231) were treated, the majority of whom had received direct acting antivirals (99%, 174/176) and had achieved sustained virological response (98%, 165/169). Conclusion Treatment targets for global elimination were missed for HBV but not for HCV. A wider European implementation of sentinel surveillance with a representative sample of sites could help monitor progress towards achieving hepatitis control targets.
A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages
Authors: Melissa Bedard, Sanne van der Niet, Elliott M. Bernard, Gregory Babunovic, Tan-Yun Cheng, Beren Aylan, Anita E. Grootemaat, Sahadevan Raman, Laure Botella, Eri Ishikawa, Mary P. O’Sullivan, Seónadh O’Leary, Jacob A. Mayfield, Jeffrey Buter, Adriaan J. Minnaard, Sarah M. Fortune, Leon O. Murphy, Daniel S. Ory, Joseph Keane, Sho Yamasaki, Maximiliano G. Gutierrez, Nicole van der Wel, D. Branch Moody
Journal: Journal of Clinical Investigation (2023)

Induction of lipid-laden foamy macrophages is a cellular hallmark of tuberculosis (TB) disease, which involves the transformation of infected phagolysosomes from a site of killing into a nutrient-rich replicative niche. Here, we show that a terpenyl nucleoside shed from Mycobacterium tuberculosis, 1-tuberculosinyladenosine (1-TbAd), caused lysosomal maturation arrest and autophagy blockade, leading to lipid storage in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside-producing M. tuberculosis, caused intralysosomal and peribacillary lipid storage patterns that matched both the molecules and subcellular locations known in foamy macrophages. Lipidomics showed that 1-TbAd induced storage of triacylglycerides and cholesterylesters and that 1-TbAd increased M. tuberculosis growth under conditions of restricted lipid access in macrophages. Furthermore, lipidomics identified 1-TbAd-induced lipid substrates that define Gaucher's disease, Wolman's disease, and other inborn lysosomal storage diseases. These data identify genetic and molecular causes of M. tuberculosis-induced lysosomal failure, leading to successful testing of an agonist of TRPML1 calcium channels that reverses lipid storage in cells. These data establish the host-directed cellular functions of an orphan effector molecule that promotes survival in macrophages, providing both an upstream cause and detailed picture of lysosome failure in foamy macrophages.
COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination — 24 U.S. Jurisdictions, October 3, 2021–December 24, 2022
Authors: Amelia G. Johnson, Lauren Linde, Akilah R. Ali, Allison DeSantis, Minchan Shi, Carolyn Adam, Brandy Armstrong, Brett Armstrong, Madison Asbell, Steven Auche, Nagla S. Bayoumi, Boudu Bingay, Melisse Chasse, Scott Christofferson, Michael Cima, Kevin Cueto, Spencer Cunningham, Janelle Delgadillo, Vajeera Dorabawila, Cherie Drenzek, Brandi Dupervil, Tonji Durant, Aaron Fleischauer, Ross Hamilton, Pauline Harrington, Liam Hicks, Jeffrey D. Hodis, Dina Hoefer, Sam Horrocks, Mikhail Hoskins, Sofia Husain, L. Amanda Ingram, Amanda Jara, Amanda Jones, F. N. U. Kanishka, Ramandeep Kaur, Saadiah I. Khan, Samantha Kirkendall, Priscilla Lauro, Shelby Lyons, Joshua Mansfield, Amanda Markelz, John Masarik, Donald McCormick, Erica Mendoza, Keeley J. Morris, Enaholo Omoike, Komal Patel, Melissa A. Pike, Tamara Pilishvili, Kevin Praetorius, Isaiah G. Reed, Rachel L. Severson, Nekabari Sigalo, Emma Stanislawski, Sarah Stich, Buddhi P. Tilakaratne, Kathryn A. Turner, Caleb Wiedeman, Allison Zaldivar, Benjamin J. Silk, Heather M. Scobie
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).*To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5)predominance.† During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5).Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65-79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65-79 years; 8.3 and ≥80 years; 4.2).In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in * https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html† National weighted estimates of weekly proportions of infections attributed to SARS-CoV-2 variants are based on CDC analyses (https://covid.cdc.gov/coviddata-tracker/#variant-proportions).Analysis periods were categorized based on variant predominance (defined as those accounting for >50% of sequenced lineages): Delta, October 3-December 18, 2021; Omicron BA.1,
A critical analysis of neuro-oncology clinical trials
Authors: Yeonju Kim, Terri S Armstrong, Mark R Gilbert, Orieta Celiku
Journal: Neuro-Oncology (2023)

Limitations in trial design, accrual, and data reporting impact efficient and reliable drug evaluation in cancer clinical trials. These concerns have been recognized in neuro-oncology but have not been comprehensively evaluated. We conducted a semi-automated survey of adult interventional neuro-oncology trials, examining design, interventions, outcomes, and data availability trends.
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Journal: JAMA Network Open (2023)

Stephanie A. Richard, PhD; Simon D. Pollett, MBBS; Anthony C. Fries, PhD; Catherine M. Berjohn, MD, MPH; Ryan C. Maves, MD; Tahaniyat Lalani, MBBS; Alfred G. Smith, MD; Rupal M. Mody, MD; Anuradha Ganesan, MBBS, MPH; Rhonda E. Colombo, MD; David A. Lindholm, MD; Michael J. Morris, MD; Nikhil Huprikar, MD; Christopher J. Colombo, MD; Cristian Madar, MD; Milissa Jones, MD, MPH; Derek T. Larson, DO; Samantha E. Bazan, AN; Katrin Mende, PhD; David Saunders, MD; Jeffrey Livezey, MD; Charlotte A. Lanteri, MD; Ann I. Scher, PhD; Celia Byrne, PhD; Jennifer Rusiecki, PhD; Evan Ewers, MD; Nusrat J. Epsi, PhD; Julia S. Rozman, BS; Caroline English; Mark P. Simons, PhD; David R. Tribble, MD; Brian K. Agan, MD; Timothy H. Burgess, MD; Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) COVID-19 Cohort Study Group; Terry Merritt; Susan Chambers; Cristin Mount; Michael Stein; Catherine Uyehara; Heidi Adams; Patrick Hickey; Edward Parmelee; Mark Fritschlanski; Tim Chao; Richard Chapleau; Monica Christian; Kelsey Lanter; Jennifer Meyer; John Iskander; Kathryn Lago
High occurrence of Enterococcus faecalis, Enterococcus faecium, and Vagococcus lutrae harbouring oxazolidinone resistance genes in raw meat-based diets for companion animals – a public health issue, Switzerland, September 2018 to May 2020
Authors: Magdalena Nüesch-Inderbinen, Lore Heyvaert, Andrea Treier, Katrin Zurfluh, Nicole Cernela, Michael Biggel, Roger Stephan
Journal: Eurosurveillance (2023)

Introduction Enterococci harbouring genes encoding resistance to florfenicol and the oxazolidinone antimicrobial linezolid have emerged among food-producing animals and meat thereof, but few studies have analysed their occurrence in raw meat-based diets (RMBDs) for pets. Aim We aimed to examine how far RMBDs may represent a source of bacteria with oxazolidinone resistance genes. Methods Fifty-nine samples of different types of RMBDs from 10 suppliers (three based in Germany, seven in Switzerland) were screened for florfenicol-resistant Gram-positive bacteria using a selective culture medium. Isolates were phenotypically and genotypically characterised. Results A total of 27 Enterococcus faecalis , Enterococcus faecium , and Vagococcus lutrae isolates were obtained from 24 of the 59 samples. The optrA , poxtA , and cfr genes were identified in 24/27, 6/27 and 5/27 isolates, respectively. Chloramphenicol and linezolid minimum inhibitory concentrations (MICs) ranged from 24.0 mg/L–256.0 mg/L, and 1.5 mg/L–8.0 mg/L, respectively. According to the Clinical and Laboratory Standards Institute (CLSI) breakpoints, 26 of 27 isolates were resistant to chloramphenicol (MICs ≥ 32 mg/L), and two were resistant to linezolid (MICs ≥ 8 mg/L). Multilocus sequence typing analysis of the 17 E. faecalis isolates identified 10 different sequence types (ST)s, with ST593 (n = 4 isolates) and ST207 (n = 2 isolates) occurring more than once, and two novel STs (n = 2 isolates). E. faecium isolates belonged to four different STs (168, 264, 822, and 1846). Conclusion The high occurrence in our sample of Gram-positive bacteria harbouring genes encoding resistance to the critical antimicrobial linezolid is of concern since such bacteria may spread from companion animals to humans upon close contact between pets and their owners.
EMT-activated secretory and endocytic vesicular trafficking programs underlie a vulnerability to PI4K2A antagonism in lung cancer
Authors: Xiaochao Tan, Guan-Yu Xiao, Shike Wang, Lei Shi, Yanbin Zhao, Xin Liu, Jiang Yu, William K. Russell, Chad J. Creighton, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2023)

Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small-molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic ligands. In the endosomal compartment, PI4K2A accelerated recycling of SPP1 receptors to complete an SPP1-dependent autocrine loop and interacted with HSP90 to prevent lysosomal degradation of AXL receptor tyrosine kinase, a driver of cell migration. These results show that EMT coordinates exocytic and endocytic vesicular trafficking to establish a therapeutically actionable hypersecretory state that drives lung cancer progression.
Photodynamic therapy: Innovative approaches for antibacterial and anticancer treatments
Authors: Marketa Kolarikova, Barbora Hosikova, Hanna Dilenko, Katerina Barton‐Tomankova, Lucie Valkova, Robert Bajgar, Lukas Malina, Hana Kolarova
Journal: Medicinal Research Reviews (2023)

Abstract Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.
Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy
Authors: Neil F. Mariados, Peter F. Orio, Zvi Schiffman, Thanh John Van, Alexander Engelman, Rizwan Nurani, Steven M. Kurtzman, Escarlata Lopez, Michael Chao, Thomas P. Boike, Alvaro A. Martinez, Glen Gejerman, John Lederer, John E. Sylvester, Gregory Bell, Douglas Rivera, Neal Shore, Katie Miller, Boris Sinayuk, Michael L. Steinberg, Daniel A. Low, Amar U. Kishan, Martin T. King
Journal: JAMA Oncology (2023)

Importance Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT. Objective To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT. Design, Setting, and Participants This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality. Main Outcomes and Measures For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%. Results Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% ( P &amp;amp;lt; .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, −10.9%; 95% 1-sided upper confidence limit, −3.5; P = .01). Conclusions and Relevance The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT. Trial Registration ClinicalTrials.gov Identifier: NCT04189913